Zinzi Alessia, Gaio Mario, Liguori Valerio, Cagnotta Cecilia, Paolino Donatella, Paolisso Giuseppe, Castaldo Giuseppe, Nicoletti Giovanni Francesco, Rossi Francesco, Capuano Annalisa, Rafaniello Concetta
Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy; Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Viale Europa s.n.c., I-88100 Catanzaro, Italy.
Pharmacol Res. 2023 Apr;190:106742. doi: 10.1016/j.phrs.2023.106742. Epub 2023 Mar 22.
Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy - tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene - is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%-78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%-42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.
嵌合抗原受体（CAR）修饰的T淋巴细胞是治疗血液系统恶性肿瘤最具创新性和前景的方法之一。CAR-T细胞疗法目前正用于治疗复发/难治性（r/r）B细胞恶性肿瘤，包括急性淋巴细胞白血病、大B细胞淋巴瘤、滤泡性淋巴瘤、多发性骨髓瘤和套细胞淋巴瘤。尽管CAR-T细胞疗法取得了前所未有的临床成功，但已获批的CAR-T细胞疗法（tisagenlecleucel、axicabtagene、lisocabtagene、idecabtagene、ciltacabtagene和brexucabtagene）的主要问题之一是其持久性的不确定性，这反过来可能导致对治疗反应微弱或无反应，进而导致恶性肿瘤复发。在此我们表明，对CAR-T细胞疗法无反应的患者的预后仍然是一项未得到满足的医疗需求。我们进行了一项系统评价和荟萃分析，收集了至少12个月随访研究中关于缓解持续时间的个体数据。我们发现，CAR-T输注后前12个月内复发的合并患病率为61%（95%CI，43%-78%）；此外，输注一年后，分析突出显示复发的合并患病率为24%（95%CI，11%-42%）。我们的结果表明，识别对CAR-T疗法反应的潜在预测生物标志物，尤其是对于受晚期血液恶性肿瘤影响的患者，可能会对符合该疗法条件的人群进行分层，识别哪些患者将受益，哪些患者不会受益，从而帮助监管机构做出决策。
